Medial temporal lobe functioning and structure in the spontaneously hypertensive rat: Comparison with Wistar–Kyoto normotensive and Wistar–Kyoto hypertensive strains

Abstract

The Spontaneously Hypertensive Rat (SHR) is used as an animal model of attention deficit hyperactivity disorder (ADHD). It displays deficits in frontostriatal functioning, but it is unclear if medial temporal lobe functioning and structure are affected. We used behavioral tasks that evaluate functioning of the amygdala and hippocampus to compare male SHR to male rats from two inbred comparator strains, the normotensive Wistar-Kyoto (WKY) and the hypertensive Wistar-Kyoto (WKHT) rat (n=8/strain). The three strains showed similar levels of amygdalarelated stimulus-reward learning during conditioned cue preference testing. In the ambiguous Tmaze task, which dissociates between spatial and habit learning, significantly more WKHT than SHR or WKY used a response (indicative of habit learning) vs. a place (indicative of spatial learning) strategy during an early probe test on day 8. During a later probe test on day 24, WKY progressed significantly from using a place strategy to a response strategy. Throughout all probe tests, a place strategy was used predominately by SHR and a response strategy by WKHT. Thus, SHR exhibited deficits in dorsal striatum-related habit learning whereas WKHT exhibited deficits in hippocampus-related spatial learning. Following behavioral testing, Fluid Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging scans were conducted in subgroups of rats from each strain (n=4/strain). FLAIR imaging detected bilateral hippocampal hyperintensities in three of four WKHT and unilateral hippocampal atrophy in one of four SHR. The association between response strategy use during the initial probe test to forage for food in the ambiguous T-maze task and bilateral hippocampal abnormalities was significant. Collectively, while medial temporal lobe functioning appears to be normal in SHR exhibiting an ADHD-like phenotype, WKHT rats display both hippocampal functioning deficits and signs of bilateral hippocampal cell loss. The latter characteristics might be used to develop a new animal model of age-or disease-related decline in hippocampal functioning.

Visual memory as a potential cognitive endophenotype of attention deficit hyperactivity disorder

“…Although volumetric reductions (Brieber et al 2007) and regional cerebral perfusion abnormalities (Kim et al 2002) have been found in medial temporal lobe structures of patients with ADHD, neuropsychological deficits associated with medial temporal lobe functioning have not been observed (Barnett et al 2005). A recent animal study using behavioral and imaging measures also demonstrated that medial temporal lobe functioning was normal in the spontaneously hypertensive rat exhibiting an ADHD-like phenotype (Wells et al 2010). Taken together, our negative findings supported the notion that medial temporal lobe functioning might not be affected in ADHD.…”

Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats

“…Prior to reward devaluation, both strains displayed similarly high rates of responding throughout 28 sessions of VI 45 sec training, indicating both strains were equally capable of exhibiting reinforcement-based goal-directed behavior. Performance of SHR before and after devaluation is consistent with performance in the ambiguous T-maze task in which SHR did not show the normal progression from using place strategies (goal-directed) early in training to using response strategies (habit) after 24 days of training [15]. SHR also failed to reach criterion levels of learning in the win-stay (habit learning) task [14].…”

Exposure to methylphenidate during infancy and adolescence in non-human animals and sensitization to abuse of psychostimulants later in life: a systematic review

“…3,21 Both works utilized cocaine self-administration after treatment with MPH and compared males of three rodent strains, namely Wistar (WIS), Wistar Kyoto (WKY) and the spontaneously hypertensive rat (SHR), the last of which is widely used as an animal genetic model for ADHD because it exhibits behavioral correlates with this disorder. 49,50 However, each study has some relevant peculiarities. For instance, Harvey et al 21 assessed DAT functionality in specific brain areas (the prefrontal cortex and striatum), while Jordan et al 3 …”